Search

Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive brain stimulation method increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help to treat addictions, but evaluation in multicenter randomized controlled trials (RCTs) is needed. We conducted a multicenter double‐blind RCT in 262 chronic smokers meeting DSM‐5 criteria for tobacco use disorder, who had made at least one prior failed attempt to quit, with 68% having made at least three failed attempts. They received three weeks of daily bilat­eral active or sham rTMS to the lateral prefrontal and insular cortices, followed by once weekly rTMS for three weeks. Each rTMS session was administered following a cue‐induced craving procedure, and participants were monitored for a total of six weeks. Those in abstinence were monitored for additional 12 weeks. The primary outcome measure was the four‐week continuous quit rate (CQR) until Week 18 in the intent‐to‐treat efficacy set, as determined by daily smoking diaries and verified by urine cotinine measures. The trial was registered at ClinicalTrials.gov (NCT02126124). In the intent‐to‐treat analysis set (N=234), the CQR until Week 18 was 19.4% following active and 8.7% following sham rTMS (X(2)=5.655, p=0.017). Among completers (N=169), the CQR until Week 18 was 28.0% and 11.7%, respectively (X(2)=7.219, p=0.007). The reduction in cigarette consumption and craving was significantly greater in the active than the sham group as early as two weeks into treatment. This study establishes a safe treatment protocol that promotes smoking cessation by stimulating relevant brain circuits. It represents the first large multicenter RCT of brain stimulation in addiction medicine, and has led to the first clearance by the US Food and Drug Administration for rTMS as an aid in smok­ing cessation for adults.

Backgrounds. Deep Transcranial Magnetic Stimulation (dTMS) is a non-invasive treatment cleared by FDA as a safe and efficient intervention for the treatment of depression and obsessive-compulsive disorder (OCD). Objectives. In this retrospective single-center study, the effects of dTMS on the electrophysiological parameters and the clinical outcomes of patients with OCD were tested. Methods. Thirty sessions of dTMS were administered to 29 OCD patients (15 female and 14 male). Quantitative electroencephalography (QEEG) recordings and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were measured at baseline and endpoint. Paired sample t-test was used to measure the change in Y-BOCS scores and QEEG activity after dTMS practice. Results. All 29 patients responded to the dTMS intervention by indicating at least 35% reduction in Y-BOCS scores. QEEG recordings revealed a significant decrease in theta, alpha and the beta rhythms. The decrease in the severity of OCD symptoms correlated with the decrease in beta activity at left central region. Conclusions. Historically, excess fast oscillations in OCD are correlated with the unresponsiveness to selective serotonin reuptake inhibitor (SSRI) treatment. We hypothesize that the decrease in the power of beta bands by deep TMS is related to the mechanism of the therapeutic response.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that has shown high efficacy in the treatment of major depressive disorder (MDD) and is increasingly utilized for various neuropsychiatric disorders. However, conventional TMS is limited to activating only a small fraction of neurons that have components parallel to the induced electric field. This likely contributes to the significant variability observed in clinical outcomes. A novel method termed rotational field TMS (rfTMS or TMS 360°) enables the activation of a greater number of neurons by reducing the sensitivity to orientation. Recruitment of a larger number of neurons offers the potential to enhance efficacy and reduce variability in the treatment of clinical indications for which neuronal recruitment and organization may play a significant role, such as MDD and stroke. The potential of the method remains to be validated in clinical trials. Here, we revisit and describe in detail the rfTMS method, its principles, mode of operation, effects on the brain, and potential benefits for clinical TMS.

Background Transcranial magnetic stimulation (TMS) is a rapidly expanding technology utilized in research and neuropsychiatric treatments. Yet, conventional TMS configurations affect primarily neurons that are aligned parallel to the induced electric field by a fixed coil, making the activation orientation-specific. A novel method termed rotational field TMS (rfTMS), where two orthogonal coils are operated with a 90° phase shift, produces rotation of the electric field vector over almost a complete cycle, and may stimulate larger portion of the neuronal population within a given brain area. Objective To compare the physiological effects of rfTMS and conventional unidirectional TMS (udTMS) in the motor cortex. Methods Hand and leg resting motor thresholds (rMT), and motor evoked potential (MEP) amplitudes and latencies (at 120% of rMT), were measured using a dual-coil array based on the H7-coil, in 8 healthy volunteers following stimulation at different orientations of either udTMS or rfTMS. Results For both target areas rfTMS produced significantly lower rMTs and much higher MEPs than those induced by udTMS, for comparable induced electric field amplitude. Both hand and leg rMTs were orientation-dependent. Conclusions rfTMS induces stronger physiologic effects in targeted brain regions at significantly lower intensities. Importantly, given the activation of a much larger population of neurons within a certain brain area, repeated application of rfTMS may induce different neuroplastic effects in neural networks, opening novel research and clinical opportunities.

Transcranial magnetic stimulation (TMS) uses magnetic pulses to induce electrical current in the underlying neuronal tissue. A variety of TMS coils exist on the market, differing primarily in configuration, orientation, and flexibility of the wire windings of the coil. Deep TMSHere we assembled all peer-reviewed publications on the H7 Coil to showcase its efficacy in: (a) various OCD patient populations (e.g., different degrees of symptom severity, treatment resistance, comorbidities) (b) other neuropsychiatric populations (e.g., addiction, major depressive disorder and autism spectrum disorder).While substantial evidence pertaining to the H7 Coil's efficacy as well as its MOA has accumulated, much work remains. In the final section of this review, we highlight areas of ongoing and future research that will further elucidate the coil's MOA as well as its full efficacy potential.

The FDA cleared deep transcranial magnetic stimulation (Deep TMS) with the H7 coil for obsessive-compulsive disorder (OCD) treatment, following a double-blinded placebo-controlled multicenter trial. Two years later the FDA cleared TMS with the D-B80 coil on the basis of substantial equivalence. In order to investigate the induced electric field characteristics of the two coils, these were placed at the treatment position for OCD over the prefrontal cortex of a head phantom, and the field distribution was measured. Additionally, numerical simulations were performed in eight Population Head Model repository models with two sets of conductivity values and three Virtual Population anatomical head models and their homogeneous versions. The H7 was found to induce significantly higher maximal electric fields (p

Chronic treatment resistant depression takes a substantial toll on patients' quality of life and alternative treatment options are limited. This prospective multicenter study evaluated the safety, tolerability and efficacy of four weeks of thrice-a-week deep transcranial magnetic stimulation (dTMS) in combination with selective serotonin reuptake inhibitors (SSRIs).Forty patients who failed to respond during a 16-week double-blind placebo controlled (DBPC) trial of dTMS or sham dTMS as monotherapy were screened and started a treatment of previously tolerable but ineffective SSRI. After ten days of medication, high frequency dTMS was added three times a week for four weeks.dTMS combined with SSRIs was well tolerated, with only headaches as a related adverse event (n = 4), which did not cause drop outs. Six patients were excluded from analysis: 1 was missing screening data and 5 received less than 10 sessions. Out of 34 patients included in this study, 12 (35.3%) patients remitted (HDRS-21 10). No significant differences were found between patients who had received sham or active dTMS in the earlier DBPC multicenter trial.This was a small scale open study of dTMS with SSRIs in patients that failed to respond during a DBPC dTMS trial, although a carryover effect cannot be excluded. Comparative efficacy of dTMS with and without SSRIs and specific dosing and protocol parameters warrant specifically-designed large-scale controlled studies.Thrice weekly dTMS at 120% motor threshold(MT), 10 HZ, 3‑s trains, 20‑s intervals, 2400 daily pulses, can augment formerly ineffective SSRI treatment.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method that is increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help treat addictions, but evaluation is required in a multicenter randomized controlled trial (RCT). METHODS: Here, we tested in chronic smokers whether repeated bilateral rTMS of the lateral prefrontal and insular cortices reduces cigarette craving and consumption and increases quit rates. This multicenter RCT included 14 sites and 262 chronic smokers who received Active or Sham rTMS. Participants received three weeks of daily rTMS sessions following cue-induced craving and were monitored up to four months. The primary outcome was the four-week continuous quit rate (CQR) measured by daily smoking diaries and verified by urine cotinine measures. Secondary outcome measures included changes in cigarette consumption and craving. This trail is registered at ClinicalTrials.gov, number NCT02126124. RESULTS: In the intent to treat analysis set, CQR was 19·4% following Active and 8·7% following Sham rTMS (χ 2 = 5·655, p=0·017). Among completers (N=169), CQR was 28·0% and 11·7%, respectively (χ 2 = 7·219, p=0·007). CQR within the first six weeks was 25·3% (Active) and 6·4% (Sham) (χ 2 = 11·885, p=0·0006), of which 63% (Active) and 50% (Sham) remained abstinent for at least four months (χ 2 =8·46, p=0·003). Significant between-group differences in cigarette consumption and craving emerged as early as two weeks into treatment. CONCLUSIONS: This study establishes a safe treatment protocol that promotes smoking cessation by stimulating the relevant brain circuits. It represents the first large multicenter RCT of brain stimulation for addiction medicine. Funded by: BrainsWay Declaration of Interest: Oscar Morales occasional reports consult work for Brainsway; Dr. Tendler reports personal fees from Brainsway, other from Advanced Mental Health Care Inc./DTMS Center LLC, outside the submitted work; Dr. Roth reports personal fees from Brainsway, outside the submitted work; In addition, Dr. Roth has a patent US 7,407,478 with royalties paid; Mr. Deutsch reports personal fees from Brainsway, during the conduct of the study; personal fees from Brainsway, outside the submitted work; David Feifel reports he is a member of Brainsway's Scientific Advisory Board (non-compensated); Dr. Duffy reports other from Brainsway, during the conduct of the study; other from Alivation Health LLC and Alivation Research LLC, outside the submitted work; Prof. Abraham Zangen is an inventor of Deep TMS coils which were patented by the NIH and other academic institutions where Abraham Zangen worked. These patents were licensed to BrainsWay and Abraham Zangen receives royalties from these patents. In addition Prof. Zangen serves as consultant for BrainsWay and has finanacial insterests in BrainsWay; Dr. Todder reports other from BRAINSWAY, during the conduct of the study; all other authors have nothing to disclose. Ethical Approval:The trial protocol (Supplementary Materials; SM 1.1) was approved by local institutional review boards and was registered at clinicaltrials.gov (NCT02126124). The study was conducted in the United States (12 sites) and Israel (two sites), with active enrollment from August 2014 through August 2019. The trial was supported by industry (BrainsWay).

Background Posttraumatic stress disorder (PTSD) is both prevalent and debilitating. While deep transcranial magnetic stimulation (dTMS) has shown preliminary efficacy, exposure therapy remains the most efficacious, though limited, treatment in PTSD. The medial prefrontal cortex (mPFC) is implicated in extinction learning, suggesting that concurrent mPFC stimulation may enhance exposure therapy. In this randomized controlled multicenter trial, the efficacy and safety of mPFC dTMS combined with a brief exposure procedure were studied in patients with PTSD. Methods Immediately following exposure to their trauma narrative, 125 outpatients were randomly assigned to receive dTMS or sham. Twelve sessions were administered over 4 weeks, with a primary end point of change in 5-week Clinician-Administered PTSD Scale for DSM-5 score. This clinical study did not include biological markers. Results Clinician-Administered PTSD Scale for DSM-5 score improved significantly in both groups at 5 weeks, though the improvement was smaller in the dTMS group (16.32) compared with the sham group (20.52; p = .027). At 9 weeks, improvement continued in Clinician-Administered PTSD Scale for DSM-5 score in both groups but remained smaller in dTMS (19.0) versus sham (24.4; p = .024). Conclusions Both groups showed significant PTSD symptom improvement, possibly from the brief script-driven imagery exposure. While our design was unable to rule out placebo effects, the magnitude and durability of improvement suggest that repeated ultrabrief exposure therapy alone may be an effective treatment for PTSD, warranting additional study. The surprising and unexpected effect in the dTMS group also suggests that repeated mPFC stimulation with the H7 coil may interfere with trauma memory–mediated extinction. Our results provide new insight for dTMS approaches for possible future avenues to treat PTSD.

Deep transcranial magnetic stimulation (dTMS) has emerged as a treatment option for adults with obsessive-compulsive disorder (OCD) who continue to exhibit impairing symptoms following an adequate response to first line interventions. Currently, little is known about the predictors or moderators of dTMS outcome for OCD. This paper examined if several theoretically relevant variables may predict and moderate treatment effects including OCD symptom severity, functional impairment, co-occurring depressive symptoms, age, gender, age of OCD onset, and family history of OCD. As part of a previously reported study, 100 patients received 29 dTMS or sham stimulation treatments over 6 weeks. dTMS was administered using a Magstim Rapid2 TMS (The Magstim Co. Ltd., Whitland, Carmarthenshire, United Kingdom) stimulator equipped with a H shaped coil design, which was specifically designed to stimulate the dorsal mPFC-ACC bilaterally. Findings suggest older participants and those with lower OCD severity and disability respond faster to both dTMS and sham stimulation. dTMS of the dorsal mPFC/ACC appeared to have larger benefits for individuals with greater OCD severity, whereas the difference between treatment arms was minimal in those with lower severity. Implications of these findings for treatment of OCD are discussed.

Background Deep transcranial magnetic stimulation (dTMS) with the H7-coil was FDA cleared for obsessive-compulsive disorder (OCD) in August 2018 based on multicenter sham-controlled studies. Here we look at the efficacy of dTMS for OCD in real world practices. Methods All dTMS clinics were asked to supply their data on treatment details and outcome measures. The primary outcome measure was response, defined by at least a 30% reduction in the Yale Brown Obsessive Compulsive Scale (YBOCS) score from baseline to endpoint. Secondary outcome measures included first response, defined as the first time the YBOCS score has met response criteria, and at least one-month sustained response. Analyses included response rate at the endpoint (after 29 dTMS sessions), number of sessions and days required to reach first response and sustained response. Results Twenty-two clinical sites with H7-coils provided data on details of treatment and outcome (YBOCS) measures from a total of 219 patients. One-hundred-sixty-seven patients who had at least one post-baseline YBOCS measure were included in the main analyses. Overall first and sustained response rates were 72.6% and 52.4%, respectively. The response rate was 57.9% in patients who had YBOCS scores after 29 dTMS sessions. First response was achieved in average after 18.5 sessions (SD = 9.4) or 31.6 days (SD = 25.2). Onset of sustained one-month response was achieved in average after 20 sessions (SD = 9.8) or 32.1 days (SD = 20.5). Average YBOCS scores demonstrated continuous reduction with increasing numbers of dTMS sessions. Conclusions In real-world clinical practice, the majority of OCD patients benefitted from dTMS, and the onset of improvement usually occurs within 20 sessions. Extending the treatment course beyond 29 sessions results in continued reduction of OCD symptoms, raising the prospect of value for extended treatment protocols in non-responders.

OCD is a chronic and disabling disease with a lifetime prevalence of 2%-3%. About 40-60% of these patients do not adequately respond to pharmacotherapy and CBT. Deep transcranial magnetic stimulation (dTMS) was shown to be safe and effective as a treatment alternative for OCD and recently received regulatory approvals. Yet it is unclear whether patients who failed numerous medications and/or CBT can still benefit from dTMS. Here, we analyzed recent data from a double-blind multicenter dTMS study and found efficacy of this novel treatment even in OCD patient cohorts who previously failed to respond to multiple medications and CBT.

Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22–68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p+0.008), resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%, p+0.013; remission: 32.6 vs. 14.6%, p+0.005). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment.

Deep transcranial magnetic stimulation (dTMS) is a relatively new technique that uses different coils for the treatment of different neuropathologies. The coils are made of soft copper windings in multiple planes that lie adjacent to the skull. They are located within a special helmet so that their magnetic fields combine and improve depth penetration. The H1 dTMS coil is designed to stimulate bilateral prefrontal cortices with greater effective stimulation over the left than the right. By positioning the left side of the coil close to the left dorsolateral prefrontal cortex (DLPFC), the H1 coil was used in a multisite study, leading to FDA approval for treatment-resistant depression. In this same position, the H1 coil was also explored as a possible treatment for negative symptoms of schizophrenia, bipolar depression, and migraine. When moved to different positions over the subject's skull, the H1 coil was also explored as a possible treatment for other conditions. Such manipulation of the H1 coil was demonstrated for PTSD and alcohol dependence by positioning it over the medial prefrontal cortex (mPFC), for anxiety by positioning it over the right prefrontal cortex (rPFC), for auditory hallucinations and tinnitus by positioning it over the temporoparietal junction (TPJ), and for Parkinson's and fatigue from multiple sclerosis (MS) by positioning it over the motor cortex (MC) and PFC. Corresponding electrical field diagrams measured with an oscilloscope through a saline-filled head are included.

Introduction Obsessive compulsive disorder (OCD) is a disabling disease with an annual prevalence of 1.2%. Currently approved medications only result in a reduction of symptoms for 40-60% of patients leaving most patients significantly affected. Symptom severity is correlated to the degree of hyperconnectivity in the cortico-stiriato-thalamic circuit and increased glucose metabolism in the anterior cingulate cortex during symptom provocation and at rest. Methods Ninety-four OCD patients who met inclusion/exclusion criteria (age 22-68, YBOCS≥20 despite SSRI treatment and/or CBT, stable on medications or therapy for at least two months) were randomized to receive active or sham treatment for twenty-nine sessions over six weeks. Deep transcranial magnetic stimulation(dTMS) was applied over the medial prefrontal(mPFC) and anterior cingulate cortices(ACC) using the H7 dTMS coil. Once the coil was in the treatment position, the patient’s symptoms were provoked using an individualized script tailored to the patient’s obsessions and compulsions. Subsequently, dTMS was administered for eighteen minutes at 100% resting motor threshold of the foot, 20HZ pulse frequency, in 2 second trains, with a 20 second inter-train interval totaling 2000 pulses. The sham coil was designed to have the same sound, scalp and facial sensation of the real coil without stimulating the brain directly. Results The mean age of the subjects was 38.7 (±11.75), 58.7%male, 78.8% Caucasian, mean age of onset was 13, 98% had failed medications approved for OCD and 68.7% had failed CBT. At the end of week 6 (the primary endpoint) the YBOCS decreased by 5.7 points (95% CI: [3.3;8.2]) in the dTMS arm and by 3.0 points (95% CI: [0.7;5.4]) in the control arm (p-value: 0.0157). Response (≥30% decrease/20% decrease in the YBOCS) rates were dTMS 38.10% in the dTMS arm and 11.11% in the sham arm (p-value:0.0033). Partial response rates were (≥20% decrease in the YBOCS) 54.76 in the dTMS arm and 26.67% in the sham arm (p-value: 0.0076). At week 10 (follow up) the YBOCS decreased by 6.2 points (95% CI: [3.6;8.7]) in the dTMS arm and by 3.8 points (95% CI: [1.4;6.2]) in the control arm (p-value: 0.0459). There were no serious adverse events related to the treatment. The most frequent adverse event, headache, did not differ in frequency between the two arms. Conclusions High frequency dTMS of the ACC was found to be an effective treatment for OCD. This approach is an additional intervention in the toolbox for treating OCD.

BackgroundRepetitive deep transcranial magnetic stimulation (dTMS) is efficacious for treatment resistant major depressive disorder (TRD) with the H1 coil by stimulating the prefrontal cortex, left more than right, at high frequency. Theoretically, the efficacy of dTMS could be optimized by simultaneously stimulating the right and left lateral prefrontal cortices (PFC) with different frequencies. This study tested the efficacy of a novel dual-channel dTMS stimulator with dual dTMS coils, in patients with TRD.MethodsThis study recruited forty-seven outpatients diagnosed with TRD, age 18-65, Hamilton Depression Rating Scale (HDRS-21) score ≥25. Each patient received 20 open label treatment sessions, five days a week for 4 consecutive weeks. Treatments were administered with the dual-channel stimulator (Brainsway Multiway dTMS device) using two channels: a. 10 Hz over the left PFC. b. 1 Hz over the right PFC. Primary and secondary efficacy outcome measures were the change in HDRS-21 score and response/remission rates at week 5, respectively.ResultsThe HDRS-21 score decreased from an average of 25.94 to 14.69 (PDiscussionThis open study shows promising results for multichannel simultaneous dTMS treatment of TRD using the Brainsway Multiway Device. Further randomized controlled studies are necessary to aid the high number of patients with TRD.Funding AcknowledgementsBrainsway Ltd.

Deep transcranial magnetic stimulation (dTMS) utilizes different H-coils to study and treat a variety of psychiatric and neurological conditions with identifiable brain targets. The availability of this technology is dramatically changing the practice of psychiatry and neurology as it provides a safe and effective way to treat even drug-resistant patients. However, up until now, no effort was made to summarize the different types of H-coils that are available, and the conditions for which they were tested. Areas covered: Here we assembled all peer reviewed publication that used one of the H-coils, together with illustrations of the effective field they generate within the brain. Currently, the technology has FDA clearance for depression and European clearance for additional disorders, and multi-center trials are exploring its safety and effectiveness for OCD, PTSD, bipolar depression and nicotine addiction. Expert commentary: Taken together with positive results in smaller scale experiments, dTMS coils represent a non-invasive way to manipulate pathological activity in different brain structures and circuits. Advances in stimulation and imaging methods can now lead to efficacious and logical treatments. This should reduce the stigma associated with mental disorders, and improve access to psychiatric treatment.

Background: Cytotoxic drugs suppress ovarian function and induce permanent or transient amenorrhea in one- to two-thirds of women. Suppression of ovarian function is effective therapy for premenopausal women with hormone receptor-positive breast cancer. Aromatase inhibition is effective for postmenopausal women with hormone receptor-positive breast cancer, but is not indicated in premenopausal women. Objective: We aim to determine whether, and for how long, ovarian estrogen production persists after chemotherapy-induced amenorrhea. Materials & methods: Serum estradiol, follicle-stimulating hormone and luteinizing hormone levels were determined in 56 breast cancer patients, 1–34 months after the onset of chemotherapyinduced amenorrhea. In 18 patients, these values were determined more than once. Postmenopausal estradiol levels are less than 10 pg/ml, follicle-stimulating hormone and luteinizing hormone greater than 20 mIU/ml. Results: The estradiol level was greater than 9 pg/ml at least once in 42 out of 56 patients. For 75 determinations, the estradiol level ranged from less than 10 to 344 pg/ml, with a median of 25 pg/ml and a mean of 41 pg/ml. Estradiol levels were not significantly correlated with either the number of months after the onset of amenorrhea at which they were drawn, or follicle-stimulating and luteinizing hormone levels. Conclusions: Ovarian estradiol production often persists for 1 year or more after chemotherapy-induced amenorrhea.